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World J Diabetes. Dec 15, 2014; 5(6): 860-867
Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.860
Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart
Jia Zhao, Rushil Randive, James A Stewart
Jia Zhao, Rushil Randive, James A Stewart, Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, United States
Author contributions: All authors contributed equally to this article.
Supported by Grants from the American Heart Association, No. SDG5310006 (JAS) and No. BGIA4150122 (JAS)
Correspondence to: James A Stewart, PhD, Assistant Professor, Department of Biological Sciences, Mississippi State University, 220 Harned Hall, 295 Lee Boulevard, PO Box GY, Mississippi State, MS 39762, United States. jstewart@biology.msstate.edu
Telephone: +1-662-325-4683 Fax: +1-662-3257939
Received: August 29, 2014
Revised: September 23, 2014
Accepted: October 31, 2014
Published online: December 15, 2014
Processing time: 106 Days and 12.4 Hours
Core Tip

Core tip: Chronic hyperglycemia is a characteristic of diabetes and one of the major causal factors of diabetic complications. In type 2 diabetes mellitus, mechanical and biochemical stimuli activated profibrotic signaling cascades resulting in myocardial fibrosis, impaired cardiac performance, and ventricular stiffness. Glucose nonenzymatically reacts with extracellular matrix (ECM) proteins forming advanced glycation end products (AGEs). AGE-modified collagen increases matrix accumulation and stiffness by engaging the receptor for AGE (RAGE), the receptor for AGE. To date, our understanding of the AGE/RAGE cascade remains imprecise. This review discusses the AGE/RAGE signaling cascade and proposes an alternate role for Rap1a in diabetic cardiovascular ECM remodeling.